The in vitro activity of gatifloxacin and levofloxacin, ciprofloxacin, penicillin, ampicillin, ampicillin-sulbactam, ceftriaxone and clarithromycin was evaluated against 173 S. pneumoniae strains (128, penicillin-susceptible strains; 32, intermediate penicillin- resistant strains and 13, penicillin-resistant strains), 163 H. influenzae strains (128, beta-lactamase non-producer; 35, beta-lactamase producers), 111 M. catarrhalis (9, beta-lactamase non-producer; 102, beta-lactamase producers), 95 Streptococcus pyogenes and 116 S. aureus strains (96, methicillin-susceptible; 20, methicillin-resistant) recovered from outpatients with respiratory tract infection. Based upon the MICs at which 50% and 90% of the isolates were inhibited we concluded that gatifloxacin proved to be the most active antibiotic against respiratory pathogens, including all the penicillin-resistant pneumococci and H. influenzae or M. catarrhalis producing beta-lactamase. Furthermore, their MICs against S. pneumoniae and methicillin-resistant S. aureus were lower than those of levofloxacin and ciprofloxacin.Therefore, this new fluoroquinolone displayed in vitro features that make it suitable for treating community-acquired respiratory tract infections.